Tuberculosis is a persistent infectious disease that threatens the health of people and numerous mammalian species throughout the world. Monitoring of Mycobacterium tuberculosis (Mtb) infections in animal models has often relied on host mortality, bacterial loads, and qualitative assessment of pathology at necropsy. These are blunt tools, largely unrelated to the markers used for diagnosis and epidemiological studies of human TB. The next generation of modeling requires matching the model and analysis to the specific research questions being asked. The lack of immunological reagents in most animal models severely limits our ability to address these questions through biomarker assessment in models more relevant than the mouse yet less expensive than non-human primates. We propose to generate reagents needed to elucidate and correlate immunological markers of tuberculosis (TB) transmission and disease development in the guinea pig. Thus, assessing tuberculosis disease stages in a relevant small mammalian model with the aid of crucial immunological reagents will greatly aid efforts into ultimately enhancing the effectiveness of current TB control efforts including a better understanding basic TB disease parameters in naturally infected mammalian models.